Targeting Ecdysone signaling for control of disease vector and other insects

Disease vector and crop pest insects are significant threats to human health and food security. Insecticides are important for insect control but face issues, including toxicity to humans, toxicity to non-target species, and development of resistant populations. There is an urgent need for new insecticides with low toxicity and high specificity, and, to circumvent resistance, with distinct mechanisms of action as compared with available insecticides. Ecdysone signaling controls insect development and reproduction. As such, disruption of ecdysone signaling can be used to control insect populations. Indeed, insecticides that affect ecdysone signaling are already in use. In this work, we will perform an arrayed Drosophila cell screen for inhibitors of ecdysone signaling. We will also engineer mosquito and Drosophila cell lines useful for determining species-specificity and for future screens. Our major research objectives are (i) to identify compounds useful for developing insecticides that inhibit ecdysone signaling and (ii) to build engineered cell lines useful for characterization of screen hit compounds and for additional future screens. This work will help advance the goal of identifying more specific and effective insecticides.